The Advanced Imaging Core of the Columbia University Medical Center Skin Diseases Research Center will provide guidance and specialized training on state-of-the-art microscopes for whole-animal, in vivo, live-cell and high-content imaging of the skin and its cells. With the advent of versatile genetically encoded fluorescent reporters and the increasing availability of multiphoton microscopes capable of imaging thick specimens and living tissues, three-dimensional, live-cell and time-lapse imaging are now essential tools in the modem biomedical arsenal. Moreover, the skin's exceptional accessibility for imaging studies provides an unprecedented opportunity to identify functional networks that link the skin's diverse cell types over broad temporal (milliseconds to months) and spatial (subcellular to whole animals) scales. The Core's long-term objective is to enable CUMCSDRC investigators to use sophisticated imaging techologies to increase the effectiveness of their skin-focused research and to accomplish studies that are not possible with traditional microscopy, biochemistry or histology. The Core's innovative features are 1) its commitment to one-on-one specialized training for Center investigators, postdoctoral fellows and graduate students, so that they develop the skills necessary to successfully employ sophisticated microscopes in their research, and 2) its personnel, who are imaging experts who have extensive experience in using in vivo and live-cell imaging of the skin and its cells. The Core's services will include multiphoton microscopy, in vivo small-animal imaging, confocal microscopy, live-cell imaging and high-content imaging. By making whole-animal in vivo and live-cell imaging approaches widely available to skin biologists, the Core seeks to revolutionize dermatologic research by shifting away from traditional histological studies of fixed tissue toward dynamic analysis of the living skin. The Specific Aims are: 1. To enable functional analysis of cell types in the intact skin with in vivo imaging. 2. To efficiently analyze cellular mechanisms in vitro by providing high-content imaging services. 3. To enable high-resolution, three-dimensional structural imaging of molecules and cells in the skin.